Overview of Enrollment Procedures Objectives: Enrollment Procedures Overview Eligibility Determination Overview of HIV Prevention Options Counseling Ring Use Instructions/Important Information

Remember: Screening Window Enrollment 56 Days

How is the enrollment visit different from other study visits? Confirm eligibility Document baseline conditions Enroll in the study No Split Visits for Enrollment

Enrollment Visit Checklist Used to guide site staff through required procedures and document that they were done.

Note: Enrollment IC will take place at the start of the visit – this includes consent for off-site visits. Long term specimen storage consent – may be a stand-alone form or included in Enrollment ICF. If stand-alone, can conduct at Enrollment or M1. Behavioral, clinical and laboratory eligibility criteria must be assessed after IC obtained. First let’s take a look at the administrative/regulatory and behavioral procedures required at Enrollment for reassessing eligibility and establishing baseline. If you are unable to see the overhead, turn to appendix 1 in your protocol. Additional notes about specimen storage consent: Malawi sites do not have long term specimen storage consent, as country regulations do not allow for this procedure If specimen storage consent is obtained at M1, the plasma archive collected at Enrollment can still be conducted. As a reminder, the specimen storage consent allows the site to keep leftover specimens (after per protocol tests have been conducted) for use in future studies. This ICF is not related to the collection of plasma archive in the study.

Enrollment Behavioral Eligibility Worksheet As with screening behavioral, available in English and local languages and items should be asked verbatim. This document serves as source for participant – reported eligibility criteria.

Note: Behavioral assessment includes Baseline Behavior Assessment, Baseline Vaginal Practices, and Enrollment ACASI

HIV Prevention Options Counseling A combined counseling session beginning at Enrollment that covers HIV/STI risk reduction and protocol adherence counseling. Continues through PUEV.

HIV Prevention Options Counseling Counselors must be certified to provide this counseling: Three mock sessions reviewed/approved by BRWG Strongly encouraged for participants to see the same counselor throughout study, if possible. Prevention options counselor should not conduct behavioral assessments or qualitative interviews during visit for the same participant. What does your team think about the feasibility of having the same counselor conduct sessions for participants throughout follow-up?

HIV Prevention Options Counseling at Enrolment Orient participant to purpose and content of sessions Help her make an informed decision about accepting or not accepting the ring as an HIV prevention method

HIV Prevention Options Counseling at Enrolment Discuss other HIV prevention strategies (building upon the risk reduction counseling provided during the screening visit) Reinforce importance of accurate reporting Begin building relationship/rapport between counselor and participant

Looking Forward: HIV Prevention Options Counseling During Follow-Up Focus on the HIV risk reduction plans developed at the previous session Explore how participant is doing with ring use and/or other HIV prevention methods Will review in more detail during phase 2 training. Counselors will also do practice follow-up sessions with Ivan before seeing your first M1.

Looking Forward: HIV Prevention Options Counseling During Follow-Up Review residual drug feedback (available M3, 6, 9, PUEV) Develop new risk reduction plan for the coming month(s) Check-in on attendance to study visits Provide informational support, as needed Will review in more detail during phase 2 training. Counselors will also do practice follow-up sessions with Ivan before seeing your first M1.

HIV Prevention Options Counseling Documentation Chart notes or site-specific worksheet Document after the session NOT a summary of procedural steps – focus on capturing participant-specific information Include enough detail to inform and guide participant’s next session Mark that counseling was done on visit checklist and whether the participant chooses to use the ring Having this item on the checklist communicates the participants choice to others without them having to re-hash this conversation with multiple staff. Note: The clinician can confirm the participant’s ring decision when the prescription is written.

Non-Acceptors Questions about reasons for declining ring for recording on RCI should be asked in a neutral and non-judgmental manner. Understanding the reasons why participants do not accept rings is a study objective

HIV Prevention Options Counseling Q/A and Mentorship ALL counseling sessions audio recorded (ppts receive verbal or written information about this) Fidelity monitoring by BRWG through systematic review of a subset of recorded sessions Monthly coaching calls to provide mentorship to counselors Ongoing training and support provided, as needed

NOTE: If indicated, perform physical and/or pelvic to follow up to any otherwise exclusionary findings from screening or newly reported symptoms. ONLY collect pelvic specimens if needed for one of these reasons. Participant diagnosed during screening with a UTI, PID or STI/RTI requiring treatment may be enrolled after completing treatment if all symptoms have resolved. Moving to the clinical procedures per Appendix 1 that are associated with reassessing eligibility and establishing baseline. If you are unable to see the overhead, follow along in appendix 1 in your protocol. Remember, medical/mens history taking is originally conducted at screening, but should be updated at Enrollment to capture any changes, confirm eligibility, and establish her baseline. Concomitant medications are also updated (assessing concomitant meds should occur during the medical history taking)

NOTE: Baseline plasma collection critical for confirming eligibility of participant who later seroconvert If blood tests meet exclusionary criteria at Screening they should be retested prior to Enrollment to allow for TAT. * = if indicated  = per local standard of care

NOTE: Highlights are revisions made in LoA#1 to allow for choice in HOPE Insertion of one study VR is also “if indicated” and will be clarified in upcoming CM

First Product Use If participant accepts ring, staff member providing it should review instructions/important information, and debrief first product use experience Check ring placement if participant expresses discomfort or want reassurance of correct placement

Same messages as in ASPIRE except: Avoid Do Not Share Storage Avoid: Women should always avoid using douches, soaps, detergents, and herbs inside the vagina. When using the ring, use of other vaginal devices is also discouraged. Some vaginal products such as condoms, lubricants, and tampons are okay to use. Talk to study staff before using any vaginal products. (old message: Other than the ring, using any vaginal products or devices [other than male and female condoms] is discouraged) Share: Do not share your ring with other women. (old message: Insert only the ring assigned to you and do not share your ring with other women) Storage: Used and dirty rings should always be stored sealed in the white bag provided to you. Store unused rings in their packaging until needed for use. Do not store used or unused rings in the refrigerator or in direct sunlight. Store out of reach of children and pets. (old message: Used and dirty rings should be stored in the bag provided to you. If you have been provided with an additional ring, store it in the packaging until needed for use.)

Definition of Enrollment Once a participant has provided written informed consent for enrollment AND Designated staff have completed the final sign off of the Eligibility Checklist (see next slide)

Visit Flow The only parts of the visit that must happen after participant is enrolled are: Provision of study VR instructions, if indicated Provision of VR and insertion, if participant accepts Digit exam, if indicated Behavioral assessments should come before ring insertion, but may happen after enrollment.

Visit Flow Be flexible! Rearrange order of procedures, when allowable per protocol, to maximize efficiencies. Think about which procedures might be able to happen concurrently: HIV Prevention Options Counseling and Final Eligibility Determination Baseline Behavioral Assessments while waiting for pharmacy to dispense the first ring Others?

What if all enrollment procedures are not completed in one day? Expected to be VERY rare If participant cannot complete the visit or enrollment procedures are missed for any reason (other than plasma – see next slide), contact the MTN-025 management team for guidance

What if plasma archive is missed? This is necessary to confirm eligibility as needed later in the trial and should always be collected prior to enrollment (before contact with study product). She should be scheduled to come in as soon as possible for the collection of this Plasma archive is the only procedures performed at enrollment that, if missed, should be made up as soon as possible. ** No other procedures are made up if missed at enrollment

Enrollment Pop Quiz Get out your quiz paper!

1. Which of these procedures is required at enrollment? Physical Exam Pelvic Exam HIV Prevention Options Counseling Provision of a Vaginal Ring

2. What is the definition of enrollment for HOPE?

3. Which of these procedures must come after ‘enrollment’? Plasma and vaginal swab collection Baseline behavioral assessments (ACASI/CRFs) Provision of VR and insertion, if participant accepts

4. True or False: HIV Risk Reduction Counseling must be done separately from HIV Prevention Options Counseling

5. Name one key element of HIV Prevention Options Counseling at Enrollment

How did you do?? 1. Required: HIV Prevention Options Counseling Enrollment Definition: Signed IC + Final Sign off of Eligibility Criteria CRF Must come after enrollment: Provision of VR and insertion, if participant accepts False: HIV risk reduction counseling is included in HIV prevention options counseling Options Counseling Key Elements: Orient participant to counseling, educate about prevention options, help make informed choice, build rapport/relationship, reinforce accurate reporting

References Protocol Section 7.3 (Enrollment Visit) Protocol Appendix 1 SSP: Section 4.4 (Enrollment Procedures) Section 12 (Counseling)

Questions?